Cell by Cell, a New Map of Mosquito Cellular Immunity to Malaria Parasites Emerges

Using techniques that allowed them to see, cell-by-cell, gene activity in 8,500 individual mosquito cells, NIAID researchers and their colleagues developed the first detailed “atlas” of the insect’s immune cells and discovered a new cell type that may play a role in helping mosquitoes resist infection by malaria-causing parasites. The information contained in this immune atlas may lead to new ways to prevent mosquitoes from transmitting malaria parasites to people. 

Carolina Barillas-Mury, M.D., Ph.D., of NIAID’s Laboratory of Malaria and Vector Research, is co-senior author on the findings, which were published in Science August 27. Previously, Dr. Barillas-Mury and her team had shown that a process called ‘immune priming’ mediated by hemocytes, the mosquito equivalent of leukocytes, could limit the ability of mosquitoes to transmit malaria, by activating the mosquito immune system to successfully fight the parasite. However, little was known about the exact cell types involved in mosquito immune responses to parasites or viruses.

In the new study, the researchers used single cell sequencing techniques to detect gene on-and-off signals in 8,500 individual cells and to identify molecular markers for each cell type. They found there were at least twice as many distinct immune cell types as previously known. One of the newly discovered immune cell types, dubbed a megacyte, had high levels of a key molecule needed for immune priming and appears to switch on additional immune responses to malaria parasites. This discovery, the investigators note, marks the first time a specific mosquito cell type has been implicated in regulating the control of malaria parasites.

The research team also used the molecular markers to find and count the cells in circulation and  cells resting on the surface of mosquito organs. This allowed them to trace how sessile mosquito immune cells are mobilized in response to infection by malaria-causing Plasmodium parasites.

  
“Defining how many cell types a mosquito has, how their gene expression changes and which cells are mobilized in response to Plasmodium infection are key steps to understand mosquito cellular immunity to malaria and to develop new strategies to disrupt disease transmission,” said Dr. Barillas-Mury. “We are currently generating antibodies to detect cell-specific markers and flow cytometry protocols to better understand the dynamics of cellular responses as malaria parasites develop in the mosquito.”

The research team included co-senior author Oliver Billker, Ph.D., previously of the Wellcome Sanger Institute, Cambridge, England, and now at Molecular Infection Medicine Sweden, Umeå University, as well as Ana Beatriz F. Barletta, Ph.D., of NIAID's Laboratory of Malaria and Vector Research (LMVR) and Gianmarco Raddi, Ph.D., previously at NIAID LMVR (NIH/OxCam MD/PhD program) and now at University of Cambridge.

Read more about NIAID research on malaria and about vectors, including mosquitoes.

Reference:

G Raddi et al. Mosquito cellular immunity at single-cell resolution. Science. DOI: 10.1126/science.abc0322 (2020).